The present invention relates to new biphenyl and biphenyl-analogous compounds, their preparation and use as pharmaceutical compositions, as integrin antagonists and in particular for the production of pharmaceutical compositions for the treatment and prophylaxis of cancer, arteriosclerosis, restenosis, osteolytic disorders such as osteoporosis, rheumatoid arthritis and ophthalmic diseases.
Integrins are heterodimeric transmembrane proteins found on the surface of cells, which play an important part in the adhesion of the cells to an extracellular matrix. They recognize extracellular glycoproteins such as fibronectin or vitronectin on the extracellular matrix by means of the RGD sequence occurring in these proteins (RGD is the single letter code for the amino acid sequence arginine-glycine-aspartate).
In general, integrins such as, for example, the vitronectin receptor, which is also called the xcex1vxcex23 receptor, or alternatively the xcex1vxcex25 receptor or the GpIIb/IIIa receptor play an important part in biological processes such as cell migration and cell-matrix adhesion and thus in diseases in which these processes are crucial steps. Cancer, osteoporosis, arteriosclerosis, restenosis (reoccurrence of stenosis after percutaneous transluminal angioplasty) and opthalmia may be mentioned by way of example.
The xcex1vxcex23 receptor occurs, for example, in large amounts on growing endothelial cells and makes possible their adhesion to an extracellular matrix. Thus the xcex1vxcex23 receptor plays an important part in angiogenesis, i.e. the formation of new blood vessels, which is a crucial prerequisite for tumor growth and metastasis formation in carcinoses. Furthermore, it is also responsible for the interaction between osteoclasts, i.e. cells resorbing mineralized tissue, and the bone structure. The first step in the degradation of bone tissue consists in the adhesion of osteoclasts to the bone. This cell-matrix interaction takes place via the xcex1vxcex23 receptor, which is why the corresponding integrin plays an important part in this process. Osteolytic diseases such as osteoporosis are induced by an inequilibrium between bone formation and bone destruction, i.e. the resorption of bone material caused by accumulation of osteoclasts predominates.
It was possible to show that the blockage of the abovementioned receptors is an important starting point for the treatment of disorders of this type. If the adhesion of growing endothelial cells to an extracellular matrix is suppressed by blocking their appropriate integrin receptors, for example, by a cyclic peptide or a monoclonal antibody, the endothelial cells die. Therefore angiogenesis does not occur, which leads to a cessation or resolution of the tumor growth (cf., for example, Brooks et al., Cell, Volume 79, 1157-1164,1994).
Moreover, the invasive properties of tumor cells and thus their capability for metastasis formation are markedly decreased if their xcex1vxcex23 receptor is blocked by an antibody (Brooks et al., J. Clin. Invest., Volume 96, 1815, 1995).
The degradation of bone tissue can be suppressed by blockage of the xcex1vxcex23 receptors of the osteoclasts, since these are then unable to accumulate on the bone in order to absorb its substance (WO 98/18461, p. 1, 1.24 to p. 2, 1.13).
By means of the blockage of the xcex1vxcex23 receptor on cells of the smooth aorta vascular musculature with the aid of integrin receptor antagonists, the migration of these cells into the neointima and thus angioplasty leading to arteriosclerosis and restenosis can be suppressed (Brown et al., Cardiovascular Res., Volume 28, 1815, 1994).
In recent years, compounds have therefore been sought which act as antagonists of integrin receptors. For example, WO 98/00395 discloses the para-substituted phenylalanine derivative (I), which shows an IC50 value of 0.13 nM in an xcex1vxcex23 receptor assay and an IC50 value of 0.16 nM in an xcex1vxcex25 receptor assay: 
The abovementioned compound (I) has a guanidine unit, by means of which the oral availability is limited on account of the relatively rapid clearance rate of the compound in the digestive tract. Thus the compound (II), for example, is preferably administered parenterally (cf. WO 98/00395, p. 25, 1. 31-32).
Furthermore, WO 98/18461, for example, discloses naphthyl compounds such as (II), which have an IC50 value in the range from 0.4 to 110 nM against the xcex1vxcex23 receptor in an SPA assay: 
Biphenyl nuclei are present in numerous pharmaceutical compositions. Experiments carried out until now to establish integrin antagonists having a biphenyl nucleus only led, however, to compounds having relatively poor activity. Thus, in addition to numerous substances included by a general formula, WO 94/12181 actually describes the biphenyl compounds (III) as antagonists of the GpIIb/IIIa receptor. The use of these compounds as xcex1vxcex23 or xcex1vxcex25 receptor antagonists is not described: 
The biphenyl compounds such as (IV) prepared by B. R. Neustadt et al. exhibit activity as xcex1vxcex23 receptor antagonists which is far below that of known integrin antagonists, which is why they are not suitable lead structures according to this document (Bioorg. Med. Chem. Lett. 8, 2395, 1998, in particular p. 2398, second paragraph): 
It was the object of the present invention to develop compounds which exhibit a high activity as integrin antagonists and in particular against the xcex1vxcex23 and/or the xcex1vxcex25 receptor.
The present object is achieved according to the invention by the substituted biphenyl compounds defined below. In particular, it has emerged that the biphenyl compounds according to the invention have a very high activity as integrin antagonists, especially against the xcex1vxcex23 and/or the xcex1vxcex25 receptor.
The present invention relates to compounds of the general formula (1) 
wherein
R1 is hydrogen, a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted aryl residue or a saturated or unsaturated, optionally substituted heterocyclic residue;
R2 is hydrogen, a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted aryl residue, a saturated or unsaturated, optionally substituted heterocyclic residue, an optionally substituted alkenyl residue, an optionally substituted alkinyl residue, xe2x80x94NR2xe2x80x2SO2R2xe2x80x3, xe2x80x94NR2xe2x80x2COOR2xe2x80x2, xe2x80x94NR2xe2x80x2COR2xe2x80x2, xe2x80x94NR2xe2x80x2CONR2xe2x80x22, or xe2x80x94NR2xe2x80x2CSNR2xe2x80x22;
R2xe2x80x2 is hydrogen, a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted aryl residue or a saturated or unsaturated, optionally substituted heterocyclic residue;
R2xe2x80x3 is a substituted or unsubstituted alkyl, alkenyl or cycloalkyl residue, a substituted or unsubstituted aryl residue or a saturated or unsaturated, optionally substituted heterocyclic residue;
U is a direct bond or a substituted or unsubstituted alkylene group;
V is a substituted or unsubstituted alkylene group, xe2x80x94NR2xe2x80x2COxe2x80x94 or xe2x80x94NR2xe2x80x2SO2xe2x80x94;
A and B are each independently of one another a 1,3- or 1,4-bridging phenylene group or a 2,4- or 2,5-bridging thienylene group each of which may optionally have additional substituents,
W is a direct bond or a substituted or unsubstituted alkylene group;
C is a direct bond or 
R3 is hydrogen, a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted aryl residue, a saturated or unsaturated, optionally substituted heterocyclic residue, an alkylamine residue, an alkylamide residue or is connected to one of R4, Y, R5 or R6, if present, with formation of an optionally substituted heterocyclic ring system which includes the nitrogen atom to which R3 is bonded, and can be saturated or unsaturated and/or can contain further heteroatoms;
R4 is hydrogen, a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted aryl residue, a saturated or unsaturated, optionally substituted heterocyclic residue, an alkylamine residue, an alkylamide residue or is connected to one of R3, Y, R5 or R6, if present, with formation of an optionally substituted heterocyclic ring system which includes the nitrogen atom to which R4 is bonded and can be saturated or unsaturated and/or can contain further heteroatoms;
X is CHNO2, CHCN, O, N or S;
Y is a direct bond or an optionally substituted alkylene or alkine group;
R5 is absent, or is hydrogen, a substituted or unsubstituted alkyl or cycloalkyl residue, xe2x80x94NO2, xe2x80x94CN, xe2x80x94COR5xe2x80x2, xe2x80x94COOR5xe2x80x2, or is connected to one of R3, Y, R4 or R6, if present, with formation of an optionally substituted carbocyclic or heterocyclic ring system which includes X and can be saturated or unsaturated and/or can contain further heteroatoms;
R5xe2x80x2 is hydrogen, a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted aryl residue or a saturated or unsaturated, optionally substituted heterocyclic residue which can be saturated or unsaturated and/or can contain further heteroatoms;
R6 is hydrogen, a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted aryl or arylcarbonyl residue, a saturated or unsaturated, optionally substituted heterocyclic residue, an alkylamine residue, an alkylamide residue or is connected to one of R3, R4, Y or R5, if present, with formation of an optionally substituted heterocyclic ring system which includes the nitrogen atom to which R6 is bonded and can be saturated or unsaturated and/or can contain further heteroatoms;
with the proviso that if A is a phenylene group and V is xe2x80x94NR2xe2x80x2COxe2x80x94 or xe2x80x94NR2xe2x80x2SO2xe2x80x94, C is not a direct bond and X is not N; and their physiologically acceptable salts and stereoisomers.
If a certain variable substituent is present more than once in a general formula (e.g. R2xe2x80x2 in xe2x80x94NR2xe2x80x2COOR2xe2x80x2) the meaning for each substituent may be chosen independently from the others out of the list given in the respective definition.
According to a preferred embodiment, the present invention relates to compounds of the general formula (1), where
R1 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclopropylmethyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, tolyl or a substituted derivative thereof;
R2 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, tolyl or a substituted derivative thereof, an optionally substituted alkenyl residue, an optionally substituted alkinyl residue, xe2x80x94NR2xe2x80x2SO2R2xe2x80x3, xe2x80x94NR2xe2x80x2COOR2xe2x80x2, xe2x80x94NR2xe2x80x2COR2xe2x80x2, xe2x80x94NR2xe2x80x2CONR2xe2x80x22 or xe2x80x94NR2xe2x80x2CSNR2xe2x80x22;
R2xe2x80x2 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclpentyl, cyclohexyl, phenyl, benzyl, tolyl or a substituted derivative thereof as, for example, 2-chlorophenyl, 2-methoxyphenyl, 2,4,6-trimethylphenyl, 4-methoxyphenyl, 4-t-butylphenyl, 2,5-dichlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 4-trifluoromethyl phenyl;
R2xe2x80x3 is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, 1,1,1-trifluorobutyl, allyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, tolyl or a substituted derivative thereof, 4-ethylphenyl, xe2x80x94C6H2(CH3)3, 2-chlorophenyl, 4-chlorophenyl, 2,5-dichlorophenyl, 4-trifluoromethylphenyl, campher-10-yl, 4-methoxyphenyl, 4-t-butylphenyl, 2,5-dimethylphenyl, 3-chlorophenyl, 2-methoxy-5-methylphenyl, 2,3,5,6-tetramethylphenyl, 2,3-dichlorophenyl, 2,4-dichlorophenyl, 2,6-dichlorophenyl, 2-naphthyl, 3-trifluoromethylphenyl, 4-fluorophenyl, 2,4-difluorophenyl, 2-chloro-6-methylphenyl, 2-chloro-4-fluorophenyl, 2,5-dimethoxyphenyl, 3,4-dimethoxyphenyl, 3-chloro-6-methoxyphenyl, 2-trifluoromethylphenyl, 2-alkylsulfonylphenyl, 2-arylsulfonylphenyl, 3-(N-acetyl-6-methoxy)anilino, 2-methoxycarbonylphenyl, 4-N-acetylphenyl, 4-ethylphenyl, 3-chloro-4-fluorphenyl, 2-fluorophenyl, 3-fluorophenyl, 2,4-difluorophenyl, 2,6-difluorophenyl, 3,4-difluorophenyl, 1-naphthyl, 4-trifluoromethoxyphenyl, 2-trifluoromethoxyphenyl, 4-chloro-2-trifluoro-phenyl, 2-trifluoromethoxy-4-bromo-phenyl, 2-fluoro-4-trifluoromethylphenyl, 8-quinolinyl or a group of the formula 
U is a direct bond,
V is an optionally substituted C1-5-alkylene group;
A is a 1,3- or 1,4-bridging phenylene group which is unsubstituted or carries at least one alkoxy or halogeno residue;
B is a 1,3- or 1,4-bridging phenylene group which is unsubstituted or carries at least one alkyl residue;
W is a direct bond or an optionally substituted C1-4-alkylene group;
C is a direct bond or 
R3 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, 1-methylpropyl, isobutyl, t-butyl, pentyl, 2-methylbutyl, isopentyl, neopentyl, hexyl, C1-4-perfluoroalkyl, cyclopropyl, cyclopropylmethyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, 4-methylcyclohexyl, 3,3,5-trimethylcyclohexyl, 5-methyl-2-hexyl, allyl, propinyl, phenyl, benzyl, tolyl, benzoyl or a substituted derivative thereof, C1-4-akylamino-C1-4-alkyl, C1-4-dialkylarino-C1-4-alkyl, amino-C1-4-alkyl, C1-4-alkyloxy-C1-4-alkyl, dialkylamino-C1-4-alkyl, amino-C1-4-alkyl, C1-4-alkyloxy-C1-4-alkyl, C1-2-perafluoroalkyl-C1-4-alkyl, 
wherein Z is hydrogen, CH3, xe2x80x94NO2 or xe2x80x94NH2, or R3 is connected to one of R4, Y, R5 or R6, if present, with formation of an optionally substituted heterocyclic 4- to 6-membered ring system which includes the nitrogen atom to which R3 is bonded and can be saturated or unsaturated and/or can contain further heteroatoms;
R4 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, 1-methyl-propyl, isobutyl, t-butyl, pentyl, 2-methyl-butyl, isopentyl, neopentyl, hexyl, C1-4-perfluoralkyl, cyclopropyl, cyclopropylmethyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, 4-methylcyclohexyl, 3,3,5-trimethylcyclohexyl, 5-methyl-2-hexyl, allyl, propinyl, phenyl, benzyl, tolyl, benzoyl or a substituted derivative thereof, C1-4-alkylainino-C1-4-alkyl, C1-4-dialkylamino-C1-4-alkyl, amino-C1-4-alkyl, C1-4-alkyloxy-C1-4-alkyl, C1-2-perfluoralkyl-C1-4-alkyl, one of the residues (a1) to (a51) or is connected to one of R3, Y, R5 or R6, if present, with formation of an optionally substituted heterocyclic 4- to 6-membered ring system which includes the nitrogen atom to which R4 is bonded and can be saturated or unsaturated and/or can contain further heteroatoms;
X is CHNO2, CHCN, O, N or S;
Y is a direct bond or a substituted or unsubstituted methylene or methine group;
R5 is absent, or is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclopropylmethyl, cyclobutyl, cyclopentyl, cyclohexyl, xe2x80x94NO2, xe2x80x94CN, xe2x80x94COR5xe2x80x2, xe2x80x94COOR5xe2x80x2 or is connected to one of R3, Y, R4 or R6, if present, with formation of an optionally substituted carbocyclic or heterocyclic 4- to 6-membered ring system which includes X and can be saturated or unsaturated and/or can contain trrther heteroatoms;
R5xe2x80x2 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, bexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, tolyl or a substituted derivative thereof;
R6 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, 1-methylpropyl, isobutyl, t-butyl, pentyl, isopentyl, 2-methylbutyl, neopentyl, hexyl, C1-4-perfluoroalkyl, cyclopropyl, cyclopropylmethyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, 4-methylcyclohexyl, 3,3,5-trimethylcyclohexyl, 5-methyl-2-hexyl, allyl, propinyl, phenyl, benzyl, tolyl, benzoyl or a substituted derivative thereof, C1-4-alkylamino-C1-4-alkyl, C1-4-dialkylamino-C1-4-alkyl, amino-C1-4-alkyl, C1-4-alkyloxy-C1-4-alkyl, C1-2-perfluoroalkyl-C1-4-alkyl, one of the residues (a1) to (a51) or is connected to one of R3, Y, R4 or R5, if present, with formation of an optionally substituted heterocyclic 4- to 6-membered ring system which includes the nitrogen atom to which R6 is bonded and can be saturated or unsaturated and/or can contain further heteroatoms.
Particularly preferred compounds of the general formula (I) according to this embodiment are those in which
R2 is xe2x80x94NR2xe2x80x2SO2R2xe2x80x3, xe2x80x94NR2xe2x80x2COOR2xe2x80x2, xe2x80x94NR2xe2x80x2COR2xe2x80x2, xe2x80x94NR2xe2x80x2CONR2xe2x80x22 or xe2x80x94NR2xe2x80x2CSNR2xe2x80x22;
R2xe2x80x2 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, tolyl or a substituted derivative thereof as, for example, 2-chlorophenyl, 2-methoxyphenyl, 2,4,6-trimethylphenyl, 4-methoxyphenyl, 4-t-butylphenyl, 2,5-dichlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 4-trifluoromethyl phenyl;
R2xe2x80x3 is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, 1,1,1-trifluorobutyl, allyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, tolyl or a substituted derivative thereof, 4-ethylphenyl, xe2x80x94C6H2(CH3)3, 2-chlorophenyl, 4-chlorophenyl, 2,5-dichlorophenyl, 4-trifluoromethylphenyl, campher-10-yl, 4-methoxyphenyl, 4-t-butylphenyl, 2,5-dimethylphenyl, 3-chlorophenyl, 2-methoxy-5-methylphenyl, 2,3,5,6-tetramethylphenyl, 2,3-dichlorophenyl, 2,4-dichlorophenyl, 2,6-dichlorophenyl, 2-naphthyl, 3-trifluoromethylphenyl, 4-fluorophenyl, 2,4-difluorophenyl, 2-chloro-6-methylphenyl, 2-chloro-4-fluorophenyl, 2,5-dimethoxyphenyl, 3,4-dimethoxyphenyl, 3-chloro-6-methoxyphenyl, 2-trifluoromethylphenyl, 2-alkylsulfonylphenyl, 2-arylsulfonylphenyl, 3-(N-acetyl-6-methoxy)anilino, 2-methoxycarbonylphenyl, 4-N-acetylphenyl, 4-ethylphenyl, 3-chloro-4-fluorphenyl, 2-fluorophenyl, 3-fluorophenyl, 2,4-difluorophenyl, 2,6-difluorophenyl, 3,4-difluorophenyl, 1-naphthyl, 4-trifluoromethoxyphenyl, 2-trifluoromethoxyphenyl, 4-chloro-2-trifluoro-phenyl, 2-trifluoromethoxy-4-bromo-phenyl, 2-fluoro-4-trifluoromethylphenyl, 8-quinolinyl or a group of the formula 
and the other substituents are as defined above.
Particularly preferred compounds of the fornula (1) are in this case those in which
R2 is xe2x80x94NR2xe2x80x2SO2R2xe2x80x3 or xe2x80x94NR2xe2x80x2COOR2xe2x80x2;
R2xe2x80x2 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, tolyl or a substituted derivative thereof as, for example; 2-chlorophenyl, 2-methoxyphenyl, 2,4,6-trimethylphenyl, 4-methoxyphenyl, 4-t-butylphenyl, 2,5-dichlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 4-trifluoromethyl phenyl;
R2xe2x80x3 is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, 1,1,1-trifluorobutyl, allyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, tolyl or a substituted derivative thereof, 4-ethylphenyl, xe2x80x94C6H2(CH3)3, 2-chlorophenyl, 4-chlorophenyl, 2,5-dichlorophenyl, 4-trifluoromethylphenyl, campher-10-yl, 4-methoxyphenyl, 4-t-butylphenyl, 2,5-dimethylphenyl, 3-chlorophenyl, 2-methoxy-5-methylphenyl, 2,3,5,6-tetramethylphenyl, 2,3-dichlorophenyl, 2,4-dichlorophenyl, 2,6-dichlorophenyl, 2-naphthyl, 3-trifluoromethylphenyl, 4-fluorophenyl, 2,4-difluorophenyl, 2-chloro-6-methylphenyl, 2-chloro-4-fluorophenyl, 2,5-dimethoxyphenyl, 3,4-dimethoxyphenyl, 3-chloro-6-methoxyphenyl, 2-trifluoromethylphenyl, 2-alkylsulfonylphenyl, 2-arylsulfonylphenyl, 3-(N-acetyl-6-methoxy)anilino, 2-methoxycarbonylphenyl, 4-N-acetylphenyl, 4-ethylphenyl, 3-chloro-4-fluorphenyl, 2-fluorophenyl, 3-fluorophenyl, 2,4-difluorophenyl, 2,6-difluorophenyl, 3,4-difluorophenyl, 1-naphthyl, 4-trifluoromethoxyphenyl, 2-trifluoromethoxyphenyl, 4-chloro-2-trifluorphenyl, 2-trifluoromethoxy-4-bromophenyl, 2-fluoro-4-trifluoromethylphenyl, 8-quinolinyl, a group of the formula 
A is a 1,3- or 1,4-bridging phenylene group optionally substituted with a methoxy or up to 2 fluororesidues;
B is an optionally methyl-substituted 1,3- or 1,4-bridging phenylene group;
C is a direct bond or 
R5 is absent, xe2x80x94NO2, xe2x80x94CN, or is connected to one of R3, Y, R4 or R6, if present, with formation of an optionally substituted carbocyclic or heterocyclic 4- to 6-membered ring system which includes X and can be saturated or unsaturated and/or can contain flirther heteroatoms;
and the other substituents are as defined above.
Additionally preferred compounds of the general formula (1) according to the present embodiment are those in which
R2 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, tolyl or a substituted derivative thereof, an optionally substituted alkenyl residue, an optionally substituted alkinyl residue,
U is a direct bond,
V is xe2x80x94CHR7xe2x80x94 or xe2x80x94CHR7(CH2)1-4xe2x80x94;
R7 is xe2x80x94NR7xe2x80x2SO2R7xe2x80x3, xe2x80x94NR7xe2x80x2COOR7xe2x80x2, xe2x80x94NR7xe2x80x2COR7xe2x80x2, xe2x80x94NR7xe2x80x2CONR7xe2x80x22 or xe2x80x94NR7xe2x80x2CSNR7xe2x80x22;
R7xe2x80x2 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, tolyl or a substituted derivative thereof as, for example, 2-chlorophenyl, 2-methoxyphenyl, 2,4,6-trimethylphenyl, 4-methoxyphenyl, 4-t-butylphenyl, 2,5-dichlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 4-trifluoromethyl phenyl;
R7xe2x80x3 is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, tolyl or a substituted derivative thereof, xe2x80x94C6H2(CH3)3, 2-chlorophenyl, 4-chlorophenyl, 2,5-dichlorophenyl, 4-trifluoromethylphenyl, campher-10-yl, 4-methoxyphenyl, 4-t-butylphenyl, 2,5-dimethylphenyl, 2,6-dimethylphenyl, 3-chlorophenyl, 2-methoxy-5-methylphenyl, 2,3,5,6-tetramethylphenyl, 2,3-dichlorophenyl, 2,6-dichlorophenyl, 2-naphthyl, 3-trifluoromethylphenyl, 4-fluorophenyl, 2,4difluorophenyl, 2-chloro-6-methylphenyl, 2-chloro-4-fluorophenyl, 2,5-dimethoxyphenyl, 3,4-dimethoxyphenyl, 3-chloro-6-methoxyphenyl, 2-trifluoromethylphenyl, 2-alkylsulfonylphenyl, 2-arylsulfonylphenyl, 3-(N-acetyl-6-methoxy)anilino, 2-methoxycarbonylphenyl, 4-N-acetylphenyl, 4-ethylphenyl, 3-chloro-4-fluorphenyl, 2-fluorophenyl, 3-fluorophenyl, 2,4-difluorophenyl, 2,6-difluorophenyl, 3,4-difluorophenyl, 1-naphthyl, 4-trifluoromethoxyphenyl, 2-trifluoromethoxyphenyl, or 8-quinolinyl, and the other substituents are as defined above.
Particularly preferred compounds of the general formula (1) in this case are those in which
R2 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, tolyl or a substituted derivative thereof, an optionally substituted alkenyl residue, an optionally substituted alkinyl residue,
U is a direct bond;
V is xe2x80x94CHR7xe2x80x94;
R7 is xe2x80x94NR7xe2x80x2SO2R7xe2x80x3 or xe2x80x94NR7xe2x80x2COOR7xe2x80x3;
R7xe2x80x2 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, tolyl or a substituted derivative thereof as, for example, 2-chlorophenyl, 2-methoxyphenyl, 2,4,6-trimethylphenyl, 4-methoxyphenyl, 4-t-butylphenyl, 2,5-dichlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 4-trifluoromethyl phenyl;
R7xe2x80x3 is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, tolyl or a substituted derivative thereof, xe2x80x94C6H2(CH3)3, 2-chlorophenyl, 4-chlorophenyl, 2,5-dichlorophenyl, 4-trifluoromethylphenyl, campher-10-yl, 4-methoxyphenyl, 4-t-butyphenyl, 2,5-dimethylphenyl, 2,6-dimethylphenyl, 3-chlorophenyl, 2-methoxy-5-methylphenyl, 2,3,5,6-tetramethylphenyl, 2,3-dichlorophenyl, 2,6-dichlorophenyl, 2-naphthyl, 3-trifluoromethylphenyl, 4-fluorophenyl, 2,4-difluorophenyl, 2-chloro-6-methylphenyl, 2-chloro-4-fluorophenyl, 2,5-dimethoxyphenyl, 3,4-dimethoxyphenyl, 3-chloro-6-methoxyphenyl, 2-trifluoromethylphenyl, 2-alkylsulfonylphenyl, 2-arylsulfonylphenyl, 3-(N-acetyl-6-methoxy)anilino, 2-methoxycarbonylphenyl, 4-N-acetylphenyl, 4-ethylphenyl, 3-chloro-4-fluorphenyl, 2-fluorophenyl, 3-fluorophenyl, 2,4-difluorophenyl, 2,6-difluorophenyl, 3,4-difluorophenyl, 1-naphthyl, 4-trifluoromethoxyphenyl, 2-trifluoromethoxyphenyl, or 8-quinolinyl,
A is a 1,3- or 1,4-bridging phenylene group optionally substituted with a methoxy or up to 2 fluoro residnes;
B is an optionally methyl-substituted 1,3- or 1,4-bridging phenylene group;
C is a direct bond or 
W is a direct bond or a xe2x80x94CH2-group
X is O or S;
Y is a direct bond
R5 is absent
and the other substituents are as defined above.
Additionally preferred compounds of the general formula (1) according to the present embodiment are those in which
R2 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, tolyl or a substituted derivative thereof, an optionally substituted alkenyl residue, an optionally substituted alkinyl residue,
U is a direct bond,
V is a C1-5-alkylene group which is optionally substituted by one or more residues R7 which are selected from the group consisting of hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, tolyl, a substituted derivative or a saturated or unsaturated, optionally substituted heterocyclic analog thereof, an optionally substituted alkenyl residue or an optionally substituted alkinyl residue;
and the other substituents are as defined above.
Particularly preferred compounds of the general formula (1) in this case are thosse in which
R2 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, tolyl or a substituted derivative thereof, an optionally substituted alkenyl residue, an optionally substituted alkinyl residue,
U is a direct bond,
V is xe2x80x94CHR7xe2x80x94;
R7 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, tolyl or a substituted derivative thereof, an optionally substituted alkenyl residue, an optionally substituted alkinyl residue,
A is a 1,3- or 1,4-bridging phenylene group optionally substituted with a methoxy or up to 2 fluoro residues
B is an optionally methyl-substituted 1,3- or 1,4-bridging phenylene group;
C is a direct bond or 
W is a direct bond or a xe2x80x94CH2-group
X ist O or S;
Y is a direct bond
R5 is absent
and the other substituents are as defined above.
According to yet another preferred embodiment, the present invention relates to compounds of the general formula (1), in which
R1 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-bputyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclopropylmethyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, tolyl or a substituted derivative thereof;
R2 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, tolyl, phenylethyl, a substituted derivative or a saturated or unsaturated, optionally substituted heterocyclic analog thereof, an optionally substituted alkenyl residue, an optionally substituted alkinyl residue;
U is a direct bond or an optionally substituted C1-3-alkylene group;
V is xe2x80x94NR8COxe2x80x94 or xe2x80x94NR8SO2xe2x80x94;
R8 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclopropylmethyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, tolyl, phenylethyl, phenylpropyl, phenoxyethyl or a substituted derivative thereof;
A is a 1,3- or 1,4-bridging phenylene group or a 2,4- or 2,5-bridging thienylene group which are unsubstituted or have at least one alkoxy or halogeno residue;
B is a 1,3- or 1,4-bridging phenylene group which is unsubstituted or has at least one alkyl residue;
W is a direct bond or an optionally substituted C1-3-alkylene group;
C is 
R3 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, 1-methylpropyl, isobutyl, t-butyl, pentyl, 2-methylbutyl, isopentyl, neopentyl, hexyl, C1-4-perfluoroalkyl, cyclopropyl, cyclopropylmethyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, 4-methylcyclohexyl, 3,3,5-trimethylcyclohexyl, 5-methyl-2-hexyl, allyl, propinyl, phenyl, benzyl, tolyl, benzoyl or a substituted derivative thereof, C1-4-alkylamino-C1-4-alkyl, C1-4-dialkylamino-C1-4-alkyl, amino-C1-4-alkyl, C1-4-alkyloxy-C1-4-alkyl, C1-2-perfluoroalkyl-C1-4-alkyl, one of the residues (a1) to (a51) or is connected to one of R4, Y or R6, if present, with formation of an optionally substituted heterocyclic 4- to 6-membered ring system which includes the nitrogen atom to which R3 is bonded and can be saturated or unsaturated and/or can contain further heteroatoms;
R4 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, 1-methyl-propyl, isobutyl, t-butyl, pentyl, 2-methyl-butyl, isopentyl, neopentyl, hexyl, C1-4-perfluoralkyl, cyclopropyl, cyclopropylmethyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, 4-methylcyclohexyl, 3,3,5-trimethylcyclohexyl, 5-methyl-2-hexyl, allyl, propinyl, phenyl, benzyl, tolyl, benzoyl or a substituted derivative thereof, C1-4-alkylamino-C1-4-alkyl, C1-4-dialkylamino-C1-4-alkyl, amino-C1-4-alkyl, C1-4-alkyloxy-C1-4-alkyl, C1-2-perfluoralkyl-C1-4-alkyl, one of the residues (a1) to (a51) or is connected to one of R3, Y or R6, if present, with formation of an optionally substituted heterocyclic 4- to 6-membered ring system which includes the nitrogen atom to which R4 is bonded and can be saturated or unsaturated and/or can contain further heteroatoms;
X is CHNO2, CHCN, O or S;
Y is a direct bond or a substituted or unsubstituted methylene or methine group;
R5 is absent;
R6 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, 1-methylpropyl, isobutyl, t-butyl, pentyl, isopentyl, 2-methylbutyl, neopentyl, hexyl, C1-4-perfluoroalkyl, cyclopropyl, cyclopropylmethyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, 4-methylcyclohexyl, 3,3,5-trimethylcyclohexyl, 5-methyl-2-hexyl, allyl, propinyl, phenyl, benzyl, tolyl, benzoyl or a substituted derivative thereof, C1-4-alkylamino-C1-4-alkyl, C1-4-dialkylamino-C1-4-alkyl, amino-C1-4-alkyl, C1-4-alkyloxy-C1-4-alkyl, C1-2-perfluoroalkyl-C1-4-alkyl, one of the residues (a1) to (a51) or is connected to one of R3, Y or R4, if present, with formation of an optionally substituted heterocyclic 4- to 6-membered ring system which includes the nitrogen atom to which R6 is bonded and can be saturated or unsaturated and/or can contain further heteroatoms.
Particularly preferred compounds of the general formula (1) according to this embodiment are those in which
U is a direct bond or xe2x80x94CHR7xe2x80x94;
R7 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, tolyl or a substituted derivative thereof, an optionally substituted alkenyl residue, an optionally substituted alkinyl residue or pyridyl;
A is a 1,3- or 1,4-bridging phenylene group optionally substituted with a methoxy group or up to 2 fluoro residues;
B is an optionally methyl-substituted 1,3- or 1,4-bridging phenylene group;
W is a direct bond or a xe2x80x94CH2-group;
C is 
X ist O or S;
Y is a direct bond
R5 is absent
and the other substituents are as defined above.
Another group of particularly preferred coumpounds of the general formula (1) according to this embodiment are those in which
A is a 2,4- or 2,5-bridging thienylene group which ist unsubstituted or has at least one alkoxy residue and the other substituents are as defined above.
Further embodiments of the invention are described below.
The present invention furthermnore relates to compounds of the general formula (1) 
wherein
R1 is hydrogen, a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted aryl residue or a saturated or unsaturated, optionally substituted heterocyclic residue;
R2 is hydrogen, a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted aryl residue, a saturated or unsaturated, optionally substituted heterocyclic residue, an optionally substituted alkenyl residue, an optionally substituted alkinyl residue, xe2x80x94NR2xe2x80x2SO2R2xe2x80x3, xe2x80x94NR2xe2x80x2COOR2xe2x80x3, xe2x80x94NR2xe2x80x2COR2xe2x80x2, xe2x80x94NR2xe2x80x2CONR2xe2x80x22 or xe2x80x94NR2xe2x80x2CSNR2xe2x80x22;
R2xe2x80x2 is hydrogen, a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted aryl residue or a saturated or unsaturated, optionally substituted heterocyclic residue;
R2xe2x80x3 is a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted aryl residue or a saturated or unsaturated, optionally substituted heterocyclic residue;
U is a direct bond or a substituted or unsubstituted alkylene group;
V is a substituted or unsubstituted alkylene group, xe2x80x94NR2xe2x80x2COxe2x80x94 or xe2x80x94NR2xe2x80x2SO2xe2x80x94;
A and B are each independently of one another a 1,3- or 1,4-bridging, optionally additionally substituted phenylene group;
W is a direct bond or a substituted or unsubstituted alkylene group;
C is a direct bond or 
R3 is hydrogen, a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted aryl residue, a saturated or unsaturated, optionally substituted heterocyclic residue, an alkylamine residue, an alkylamide residue or is connected to one of R4, Y, R5 or R6, if present, with formation of an optionally substituted heterocyclic ring system which includes the nitrogen atom to which R3 is bonded, and can be saturated or unsaturated and/or can contain further heteroatoms;
R4 is hydrogen, a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted aryl residue, a saturated or unsaturated, optionally substituted heterocyclic residue, an alkylamine residue, an alkylamide residue or is connected to one of R3, Y, R5 or R6, if present, with formation of an optionally substituted heterocyclic ring system which includes the nitrogen atom to which R4 is bonded and can be saturated or unsaturated and/or can contain further heteroatoms;
X is CHNO2, CHCN, O, N or S;
Y is a direct bond or an optionally substituted alkylene or alkine group;
R5 is absent, or is hydrogen, a substituted or unsubstituted alkyl or cycloalkyl residue, xe2x80x94NO2, xe2x80x94CN, xe2x80x94COR5xe2x80x2, xe2x80x94COOR5xe2x80x2, or is connected to one of R3, Y, R4 or R6, if present, with formation of an optionally substituted carbocyclic or heterocyclic ring system which includes X and can be saturated or unsaturated and/or can contain further heteroatoms;
R5xe2x80x2 is hydrogen, a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted aryl residue or a saturated or unsaturated, optionally substituted heterocyclic residue which can be saturated or unsaturated and/or can contain further heteroatoms;
R6 is hydrogen, a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted aryl residue, a saturated or unsaturated, optionally substituted heterocyclic residue, an alkylamine residue, an alkylamide residue or is connected to one of R3, R4, Y or R5, if present, with formation of an optionally substituted heterocyclic ring system which includes the nitrogen atom to which R6 is bonded and can be saturated or unsaturated and/or can contain further heteroatoms;
with the proviso that if V is xe2x80x94NR2xe2x80x2COxe2x80x94 or xe2x80x94NR2xe2x80x2SO2xe2x80x94, C is not a direct bond and X is not N; and their physiologically acceptable salts and stereoisomers.
According to a preferred embodiment, the present invention relates to compounds of the general formula (1), where
R1 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclopropylmethyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, tolyl or a substituted derivative thereof;
R2 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, tolyl or a substituted derivative thereof, an optionally substituted alkenyl residue, an optionally substituted alkinyl residue, xe2x80x94NR2xe2x80x2SO2R2xe2x80x3, xe2x80x94NR2xe2x80x2COOR2xe2x80x3, xe2x80x94NR2xe2x80x2COR2xe2x80x2, xe2x80x94NR2xe2x80x2CONR2xe2x80x22 or xe2x80x94NR2xe2x80x2CSNR2xe2x80x22;
R2xe2x80x2 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclpentyl, cyclohexyl, phenyl, benzyl, tolyl or a substituted derivative thereof as, for example, 2-chlorophenyl, 2-methoxyphenyl, 2,4,6-trimethylphenyl, 4-methoxyphenyl, 4-t-butylphenyl, 2,5-dichlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 4-trifluoromethyl phenyl;
R2xe2x80x3 is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, tolyl or a substituted derivative thereof, xe2x80x94C6H2(CH3)3, 2-chlorophenyl, 4-chlorophenyl, 2,5-dichlorophesnyl, 4-trifluoromethylphenyl, campher-10-yl, 4-methoxyphenyl, 4-t-butylphenyl, 2,5-dimethylphenyl, 3-chlorophenyl, 2-methoxy-5-methylphenyl, 2,3,5,6-tetramethylphenyl, 2,3-dichlorophenyl, 2,6-dichlorophenyl, 2-naphthyl, 3-trifluoromethylphenyl, 4-fluorophenyl, 2,4-difluorophenyl, 2-chloro-6-methylphenyl, 2-chloro-4-fluorophenyl, 2,5-dimethoxyphenyl, 3,4-dimethoxyphenyl, 3-chloro-6-methoxyphenyl, 2-trifluoromethylphenyl, 2-alkylsulfonylphenyl, 2-arylsulfonylphenyl, 3-(N-acetyl-6-methoxy)anilino, 2-methoxycarbonylphenyl, 4-N-acetylphenyl, 4-ethylphenyl, 3-chloro-4-fluorphenyl, 2-fluorophenyl, 3-fluorophenyl, 2,4-difluorophenyl, 2,6-difluorophenyl, 3,4-difluorophenyl, 1-naphthyl, 4-trifluoromethoxyphenyl, 2-trifluoromethoxyphenyl, or 8-quinolinyl,
U is a direct bond,
V is an optionally substituted C1-5-alkylene group;
A is a 1,3- or 1,4-bridging phenylene group which is unsubstituted or carries at least one alkoxy residue;
B is a 1,3- or 1,4-bridging phenylene group which is unsubstituted or carries at least one alkyl residue;
W is a direct bond or an optionally substituted C1-4-alkylene group;
C is a direct bond or 
R3 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclopropylmethyl, cyclobutyl, cyclopentyl, cyclohexyl, 4-methylcyclohexyl, 3,3,5-trimethylcyclohexyl, 5-methyl-2-hexyl, phenyl, benzyl, tolyl or a substituted derivative thereof, C1-4-alkylamino-C1-4-alkyl, C1-4-dialkylamino-C1-4-alkyl, amino-C1-4-alkyl, C1-4-alkyloxy-C1-4-alkyl, dialkylamino-C1-4-alkyl, amino-C1-4-alkyl, C1-4-alkyloxy-C1-4-alkyl, 
or is connected to one of R4, Y, R5 or R6, if present, with formation of an optionally substituted heterocyclic 4- to 6-membered ring system which includes the nitrogen atom to which R3 is bonded and can be saturated or unsaturated and/or can contain further heteroatoms;
R4 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclopropylmethyl, cyclobutyl, cyclopentyl, cyclohexyl, 4-methylcyclohexyl, 3,3,5-trimethylcyclohexyl, 5-methyl-2-hexyl, phenyl, benzyl, tolyl or a substituted derivative thereof, C1-4-alkylamino-C1-4-alkyl, C1-4-dialkylamino-C1-4-alkyl, amino-C1-4-alkyl, C1-4-alkyloxy-C1-4-alkyl, one of the residues (a1) to (a29) or is connected to one of R3, Y, R5 or R6, if present, with formation of an optionally substituted heterocyclic 4- to 6-membered ring system which includes the nitrogen atom to which R4 is bonded and can be saturated or unsaturated and/or can contain further heteroatoms;
X is CHNO2, CHCN, O, N or S;
Y is a direct bond or a substituted or unsubstituted methylene or methine group;
R5 is absent, or is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclopropylmethyl, cyclobutyl, cyclopentyl, cyclohexyl, xe2x80x94NO2, xe2x80x94CN, xe2x80x94COR5xe2x80x2, xe2x80x94COOR5xe2x80x2 or is connected to one of R3, Y, R4 or R6, if present, with formation of an optionally substituted carbocyclic or heterocyclic 4- to 6-membered ring system which includes X and can be saturated or unsaturated and/or can contain further heteroatoms;
R5xe2x80x2 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, tolyl or a substituted derivative thereof;
R6 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclopropylmethyl, cyclobutyl, cyclopentyl, cyclohexyl, 4-methylcyclohexyl, 3,3,5-trimethylcyclohexyl, 5-methyl-2-hexyl, phenyl, benzyl, tolyl or a substituted derivative thereof, C1-4-alkylamino-C1-4-alkyl, C1-4-dialkylamino-C1-4-alkyl, amino-C1-4-alkyl, C1-4-alkyloxy-C1-4-alkyl, one of the residues (a1) to (a29) or is connected to one of R3, Y, R4 or R5, if present, with formation of an optionally substituted heterocyclic 4- to 6-membered ring system which includes the nitrogen atom to which R6 is bonded and can be saturated or unsaturated and/or can contain further heteroatoms.
Particularly preferred compounds of the general formula (I) according to this embodiment are those in which
R2 is xe2x80x94NR2xe2x80x2SO2R2xe2x80x3, xe2x80x94NR2xe2x80x2COOR2xe2x80x3, xe2x80x94NR2xe2x80x2COR2xe2x80x2, xe2x80x94NR2xe2x80x2CONR2xe2x80x22 or xe2x80x94NR2xe2x80x2CSNR2xe2x80x22;
R2xe2x80x2 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, tolyl or a substituted derivative thereof as, for example, 2-chlorophenyl, 2-methoxyphenyl, 2,4,6-trimethylphenyl, 4-methoxyphenyl, 4-t-butylphenyl, 2,5-dichlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 4-trifluoromethyl phenyl;
R2xe2x80x3 is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, tolyl or a substituted derivative thereof, xe2x80x94C6H2(CH3)3, 2-chlorophenyl, 4-chlorophenyl, 2,5-dichlorophenyl, 4-trifluoromethylphenyl, campher-10-yl, 4-methoxyphenyl, 4-t-butylphenyl, 2,5-dimethylphenyl, 3-chlorophenyl, 2-methoxy-5-methylphenyl, 2,3,5,6-tetramethylphenyl, 2,3-dichlorophenyl, 2,6-dichlorophenyl, 2-naphthyl, 3-trifluoromethylphenyl, 4-fluorophenyl, 2,4-difluorophenyl, 2-chloro-6-methylphenyl, 2-chloro-4-fluorophenyl, 2,5-dimethoxyphenyl, 3,4-dimethoxyphenyl, 3-chloro-6-methoxyphenyl, 2-trifluoromethylphenyl, 2-alkylsulfonylphenyl, 2-arylsulfonylphenyl, 3-(N-acetyl-6-methoxy)anilino, 2-methoxycarbonylphenyl, 4-N-acetylphenyl, 4-ethylphenyl, 3-chloro-4-fluorphenyl, 2-fluorophenyl, 3-fluorophenyl, 2,4-difluorophenyl, 2,6-difluorophenyl, 3,4-difluorophenyl, 1-naphthyl, 4-trifluoromethoxyphenyl, 2-trifluoromethoxyphenyl, or 8-quinolinyl,
and the other substituents are as defined above.
Particularly preferred compounds of the formula (1) are in this case those in which
R2 is xe2x80x94NR2xe2x80x2SO2R2xe2x80x3 or xe2x80x94NR2xe2x80x2COOR2xe2x80x3;
R2xe2x80x2 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, tolyl or a substituted derivative thereof as, for example, 2-chlorophenyl, 2-methoxyphenyl, 2,4,6-trimethylphenyl, 4-methoxyphenyl, 4-t-butylphenyl, 2,5-dichlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 4-trifluoromethyl phenyl;
R2xe2x80x3 is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, tolyl or a substituted derivative thereof, xe2x80x94C6H2(CH3)3, 2-chlorophenyl, 4-chlorophenyl, 2,5-dichlorophenyl, 4-trifluoromethylphenyl, campher-10-yl, 4-methoxyphenyl, 4-t-butylphenyl, 2,5-dimethylphenyl, 3-chlorophenyl, 2-methoxy-5-methylphenyl, 2,3,5,6-tetramethylphenyl, 2,3-dichlorophenyl, 2,6-dichlorophenyl, 2-naphthyl, 3-trifluoromethylphenyl, 4-fluorophenyl, 2,4-difluorophenyl, 2-chloro-6-methylphenyl, 2-chloro-4-fluorophenyl, 2,5-dimethoxyphenyl, 3,4-dimethoxyphenyl, 3-chloro-6-methoxyphenyl, 2-trifluoromethylphenyl, 2-alkylsulfonylphenyl, 2-arylsulfonylphenyl, 3-(N-acetyl-6-methoxy)anilino, 2-methoxycarbonylphenyl, 4-N-acetylphenyl, 4-ethylphenyl, 3-chloro-4-fluorphenyl, 2-fluorophenyl, 3-fluorophenyl, 2,4-difluorophenyl, 2,6-difluorophenyl, 3,4-difluorophenyl, 1-naphthyl, 4-trifluoromethoxyphenyl, 2-trifluoromethoxyphenyl, or 8-quinolinyl,
A is an optionally methoxy-substituted 1,3- or 1,4-bridging phenylene group;
B is an optionally methyl-substituted 1,3- or 1,4-bridging phenylene group;
C is 
W is a direct bond;
X is O or S;
Y is a direct bond;
R5 is absent;
and the other substituents are as defined above.
Additionally preferred compounds of the general formula (1) according to the present embodiment are those in which
R2 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, tolyl or a substituted derivative thereof, an optionally substituted alkenyl residue, an optionally substituted alkinyl residue,
U is a direct bond,
V is xe2x80x94CHR7xe2x80x94 or xe2x80x94CHR7(CH2)1-4xe2x80x94;
R7 is xe2x80x94NR7xe2x80x2SO2R7xe2x80x3, xe2x80x94NR7xe2x80x2COOR7xe2x80x2, xe2x80x94NR7xe2x80x2COR7xe2x80x2, xe2x80x94NR7xe2x80x2CONR7xe2x80x22 or xe2x80x94NR7xe2x80x2CSNR7xe2x80x22;
R7xe2x80x2 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, tolyl or a substituted derivative thereof as, for example, 2-chlorophenyl, 2-methoxyphenyl, 2,4,6-trimethylphenyl, 4-methoxyphenyl, 4-t-butylphenyl, 2,5-dichlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 4-trifluoromethyl phenyl;
R7xe2x80x3 is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, tolyl or a substituted derivative thereof, xe2x80x94C6H2(CH3)3, 2-chlorophenyl, 4-chlorophenyl, 2,5-dichlorophenyl, 4-trifluoromethylphenyl, campher-10-yl, 4-methoxyphenyl, 4-t-butylphenyl, 2,5-dimethylphenyl, 3-chlorophenyl, 2-methoxy-5-methylphenyl, 2,3,5,6-tetramethylphenyl, 2,3-dichlorophenyl, 2,6-dichlorophenyl, 2-naphthyl, 3-trifluoromethylphenyl, 4-fluorophenyl, 2,4-difluorophenyl, 2-chloro-6-methylphenyl, 2-chloro-4-fluorophenyl, 2,5-dimethoxyphenyl, 3,4-dimethoxyphenyl, 3-chloro-6-methoxyphenyl, 2-trifluoromethylphenyl, 2-alkylsulfonylphenyl, 2-arylsulfonylphenyl, 3-(N-acetyl-6-methoxy)anilino, 2-methoxycarbonylphenyl, 4-N-acetylphenyl, 4-ethylphenyl, 3-chloro-4-fluorphenyl, 2-fluorophenyl, 3-fluorophenyl, 2,4-difluorophenyl, 2,6-difluorophenyl, 3,4-difluorophenyl, 1-naphthyl, 4-trifluoromethoxyphenyl, 2-trifluoromethoxyphenyl, or 8-quinolinyl,
and the other substituents are as defined above.
Particularly preferred compounds of the general formula (1) in this case are those in which
R2 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, tolyl or a substituted derivative thereof, an optionally substituted alkenyl residue, an optionally substituted alkinyl residue,
U is a direct bond;
V is xe2x80x94CHR7xe2x80x94;
R7 is xe2x80x94NR7xe2x80x2SO2R7xe2x80x3 or xe2x80x94NR7xe2x80x2COOR7xe2x80x3;
R7xe2x80x2 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, tolyl or a substituted derivative thereof as, for example, 2-chlorophenyl, 2-methoxyphenyl, 2,4,6-trimethylphenyl, 4-methoxyphenyl, 4-t-butylphenyl, 2,5-dichlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 4-trifluoromethyl phenyl;
R7xe2x80x3 is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pepntyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, tolyl or a substituted derivative thereof, xe2x80x94C6H2(CH3)3, 2-chlorophenyl, 4-chlorophenyl, 2,5-dichlorophenyl, 4-trifluoromethylphenyl, campher-10-yl, 4-methoxyphenyl, 4-t-butyphenyl, 2,5-dimethylphenyl, 3-chlorophenyl, 2-methoxy-5-methylphenyl, 2,3,5,6-tetramethylphenyl, 2,3-dichlorophenyl, 2,6-dichlorophenyl, 2-naphthyl, 3-trifluoromethylphenyl, 4-fluorophenyl, 2,4-difluorophenyl, 2-chloro-6-methylphenyl, 2-chloro-4-fluorophenyl, 2,5-dimethoxyphenyl, 3,4-dimethoxyphenyl, 3-chloro-6-methoxyphenyl, 2-trifluoromethylphenyl, 2-alkylsulfonylphenyl, 2-arylsulfonylphenyl, 3-(N-acetyl-6-methoxy)anilino, 2-methoxycarbonyl phenyl, 4-N-acetylphenyl, 4-ethylphenyl, 3-chloro-4-fluorphenyl, 2-fluorophenyl, 3-fluorophenyl, 2,4-difluorophenyl, 2,6-difluorophenyl, 3,4-difluorophenyl, 1-naphthyl, 4-trifluoromethoxyphenyl, 2-trifluoromethoxyphenyl, or 8-quinolinyl,
A is an optionally methoxy-substituted 1,3- or 1,4-bridging phenylene group;
B is an optionally methyl-substituted 1,3- or 1,4-bridging phenylene group;
C is 
W is a direct bond;
X is O or S;
Y is a direct bond;
R5 is absent;
and the other substituents are as defined above.
Additionally preferred compounds of the general formula (1) according to the present embodiment are those in which
R2 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, tolyl or a substituted derivative thereof, an optionally substituted alkenyl residue, an optionally substituted alkinyl residue,
U is a direct bond,
V is a C1-5-alkylene group which is optionally substituted by one or more residues R7 which are selected from the group consisting of hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, tolyl, a substituted derivative or a saturated or unsaturated, optionally substituted heterocyclic analog thereof, an optionally substituted alkenyl residue or an optionally substituted alkinyl residue;
and the other substituents are as defined above.
Particularly preferred compounds of the general formula (1) in this case are those in which
R2 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, tolyl or a substituted derivative thereof, an optionally substituted alkenyl residue, an optionally substituted alkinyl residue,
U is a direct bond,
V is xe2x80x94CHR7xe2x80x94;
R7 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, tolyl or a substituted derivative thereof, an optionally substituted alkenyl residue, an optionally substituted alkinyl residue,
A is an optionally methoxy-substituted 1,3- or 1,4-bridging phenylene group;
B is an optionally methyl-substituted 1,3- or 1,4-bridging phenylene group;
C is 
W is a direct bond;
X is O or S;
Y is a direct bond;
R5 is absent;
and the other substituents are as defined above.
According to yet another preferred embodiment, the present invention relates to compounds of the general formula (1), in which
R1 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclopropylmethyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, tolyl or a substituted derivative thereof;
R2 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, tolyl, phenylethyl, a substituted derivative or a saturated or unsaturated, optionally substituted heterocyclic analog thereof, an optionally substituted alkenyl residue, an optionally substituted alkinyl residue;
U is a direct bond or an optionally substituted C1-3-alkylene group;
V is xe2x80x94NR8COxe2x80x94 or xe2x80x94NR8SO2xe2x80x94;
R8 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclopropylmethyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, tolyl, phenylethyl, phenylpropyl, phenoxyethyl or a substituted derivative thereof;
A is a 1,3- or 1,4-bridging phenylene group which is unsubstituted or has at least one alkoxy residue;
B is a 1,3- or 1,4-bridging phenylene group which is unsubstituted or has at least one alkyl residue;
W is a direct bond or an optionally substituted C1-3-alkylene group;
C is 
R3 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclopropylmethyl, cyclobutyl, cyclopentyl, cyclohexyl, 4-methylcyclohexyl, 3,3,5-trimethylcyclohexyl, 5-methyl-2-hexyl, phenyl, benzyl, tolyl or a substituted derivative thereof, C1-4-alkylamino-C1-4-alkyl, C1-4-dialkylamino-C1-4-alkyl, amino-C1-4-alkyl, C1-4-alkyloxy-C1-4-alkyl, one of the residues (a1) to (a29) or is connected to one of R4, Y or R6, if present, with formation of an optionally substituted heterocyclic 4- to 6-membered ring system which includes the nitrogen atom to which R3 is bonded and can be saturated or unsaturated and/or can contain further heteroatoms;
R4 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclopropylmethyl, cyclobutyl, cyclopentyl, cyclohexyl, 4-methylcyclohexyl, 3,3,5-trimethylcyclohexyl, 5-methyl-2-hexyl, phenyl, benzyl, tolyl or a substituted derivative thereof, C1-4-alkylamino-C1-4-alkyl, C1-4-dialkylamino-C1-4-alkyl, amino-C1-4-alkyl, C1-4-alkyloxy-C1-4-alkyl, one of the residues (a1) to (a29) or is connected to one of R3, Y or R6, if present, with formation of an optionally substituted heterocyclic 4- to 6-membered ring system which includes the nitrogen atom to which R4 is bonded and can be saturated or unsaturated and/or can contain further heteroatoms;
X is CHNO2, CHCN, O or S;
Y is a direct bond or a substituted or unsubstituted methylene or methine group;
R5 is absent;
R6 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclopropylmethyl, cyclobutyl, cyclopentyl, cyclohexyl, 4-methylcyclohexyl, 3,3,5-trimethylcyclohexyl, 5-methyl-2-hexyl, phenyl, benzyl, tolyl or a substituted derivative thereof, C1-4-alkylamino-C1-4-alkyl, C1-4-dialkylamino-C1-4-alkyl, amino-C1-4-alkyl, C1-4-alkyloxy-C1-4-alkyl, one of the residues (a1) to (a29) or is connected to one of R3, Y or R4, if present, with formation of an optionally substituted heterocyclic 4- to 6-membered ring system which includes the nitrogen atom to which R6 is bonded, and can be saturated or unsaturated and/or can contain further heteroatoms.
Particularly preferred compounds of the general formula (1) according to this embodiment are those in which
U is a direct bond or xe2x80x94CHR7xe2x80x94;
R7 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, tolyl or a substituted derivative thereof, an optionally substituted alkenyl residue, an optionally substituted alkinyl residue;
A is an optionally methoxy-substituted 1,3- or 1,4-bridging phenylene group;
B is an optionally methyl-substituted 1,3- or 1,4-bridging phenylene group;
W is a direct bond;
Y is a direct bond;
and the other substituents are as defined above.
The present invention fairthermore relates to a process for the preparation of the above-mentioned compounds having the general formula (1), 
which comprises the steps
a) reaction of a carboxylic acid derivative of the formula (2) 
wherein
P is a conventional protective group, a solid phase used for carrying out a solid-phase reaction or R1 is as defined in claim 1;
A is a phenylene group which is 1,3- or 1,4-substituted or a thienylene group which is 2,4- or 2,5-substituted with respect to V and L and optionally has additional residues;
L is xe2x80x94H, xe2x80x94F, xe2x80x94Cl, xe2x80x94Br, xe2x80x94I, xe2x80x94SCN, xe2x80x94N2+ or an organometallic residue; and the other residues are as defined above;
with a phenyl compound of the formula (3)
Mxe2x80x94Bxe2x80x94Wxe2x80x94Dxe2x80x83xe2x80x83(3)
wherein
M is xe2x80x94H, xe2x80x94I, xe2x80x94N2+, xe2x80x94COOCOBNO2 or an organometallic residue;
B is a phenylene group which is 1,3- or 1,4-substituted with respect to M and Wxe2x80x94D and optionally has additional residues;
W is as defined in claim 1;
D is xe2x80x94NO2, xe2x80x94NH2 or xe2x80x94CHO;
to give a biphenyl or thienyl-phenyl compound of the formula (4) 
where the residues are as defined above;
b) conversion of the residue D into the corresponding amino group, if D is not xe2x80x94NH2; and
c) if appropriate, derivatization of nitrogen atoms present at preferred times within the preparation process and/or the conversion of the compound obtained into the free acid and/or the conversion of the compound obtained into one of its physiologically acceptable salts by reaction with an inorganic or organic base or acid.
In the process according to the invention all steps can be carried out during the bonding of the carboxylic acid derivative of the formula (2) to a solid phase.
Furthermore, according to a preferred embodiment of the process according to the invention a carboxylic acid derivative of the formula (2), in which
L is xe2x80x94F, xe2x80x94Cl, xe2x80x94Br or xe2x80x94I
and the other residues are as defined above, is reacted with a phenyl compound of the formula (3), in which
M is an organometallic residue;
and the other residues are as defined above, in the presence of a palladium compound and of a phosphane.
Preferably, in the above process according to the invention a carboxylic acid derivative of the formula (2) is employed which contains a sulfonamide or carbamate group which was formed by reaction of an amino group of the corresponding precursor of the carboxylic acid derivative of the formula (2) with a sulfonyl halide or a carbamoyl halide.
It is furthermore preferred that in the above process according to the invention, in the case in which D is xe2x80x94NO2 in the compound of the formula (4), the conversion of D into an amino group is carried out in the presence of a tin(II) compound. It is furthermore preferred that in the above process according to the invention, in the case in which D is xe2x80x94CHO in the compound of the formula (4), the conversion of D into an amino group by reaction with an amine is carried out under reducing conditions.
It is moreover preferred that the compound of the formula (4) in which D is an amino group is converted into a urea or thiourea unit by a reaction of this amino group with a carbonic acid derivative or thiocarbonic acid derivative and a subsequent reaction with an amine of the formula NHR4R6, where R4 and R6 are as defined above.
The present invention furthermore relates to a pharmaceutical composition which contains at least one of the compounds defined above.
The present invention also relates to the use of the compounds described above for the production of pharmaceutical compositions having integrin-antagonistic action.
The present invention furthermore relates to the use of compounds of the general formula (1) 
wherein
R1 is hydrogen, a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted aryl residue or a saturated or unsaturated, optionally substituted heterocyclic residue;
R2 is hydrogen, a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted aryl residue, a saturated or unsaturated, optionally substituted heterocyclic residue, an optionally substituted alkenyl residue, an optionally substituted alkinyl residue, xe2x80x94NR2xe2x80x2SO2R2xe2x80x3, xe2x80x94NR2xe2x80x2COOR2xe2x80x2, xe2x80x94NR2xe2x80x2COR2xe2x80x2, xe2x80x94NR2xe2x80x2CONR2xe2x80x22 or xe2x80x94NR2xe2x80x2CSNR2xe2x80x22;
R2 is hydrogen, a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted aryl residue or a saturated or unsaturated, optionally substituted heterocyclic residue;
R2xe2x80x3 is a substituted or unsubstituted alkyl, alkenyl or cycloalkyl residue, a substituted or unsubstituted aryl residue or a saturated or unsaturated, optionally substituted heterocyclic residue;
U is a direct bond or a substituted or unsubstituted alkylene group;
V is a substituted or unsubstituted alkylene group, xe2x80x94NR2xe2x80x2COxe2x80x94 or xe2x80x94NR2xe2x80x2SO2xe2x80x94;
A and B are each independently of one another a 1,3- or 1,4-bridging phenylene group or a 2,4- or 2,5-bridging thienylene group each of which may optionally have additional substituents,
W is a direct bond or a substituted or unsubstituted alkylene group;
C is a direct bond or 
R3 is hydrogen, a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted aryl residue, a saturated or unsaturated, optionally substituted heterocyclic residue, an alkylamine residue, an alkylamide residue or is connected to one of R4, Y, R5 or R6, if present, with formation of an optionally substituted heterocyclic ring system which includes the nitrogen atom to which R3 is bonded, and can be saturated or unsaturated and/or can contain further heteroatoms;
R4 is hydrogen, a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted aryl residue, a saturated or unsaturated, optionally substituted heterocyclic residue, an alkylarnine residue, an alkylamide residue or is connected to one of R3, Y, R5 or R6, if present, with formation of an optionally substituted heterocyclic ring system which includes the nitrogen atom to which R4 is bonded and can be saturated or unsaturated and/or can contain further heteroatoms;
X is CHNO2, CHCN, O, N or S;
Y is a direct bond or an optionally substituted alkylene or alkine group;
R5 is absent, or is hydrogen, a substituted or unsubstituted alkyl or cycloalkyl residue, xe2x80x94NO2, xe2x80x94CN, xe2x80x94COR5xe2x80x2, xe2x80x94COOR5xe2x80x2, or is connected to one of R3, Y, R4 or R6, if present, with formation of an optionally substituted carbocyclic or heterocyclic ring system which includes X and can be saturated or unsaturated and/or can contain further heteroatoms;
R5xe2x80x2 is hydrogen, a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted aryl residue or a saturated or unsaturated, optionally substituted heterocyclic residue which can be saturated or unsaturated and/or can contain further heteroatoms;
R6 is hydrogen, a substituted or unsubstituted alkyl or cycloalkyl residue, a substituted or unsubstituted aryl or arylcarbonyl residue, a saturated or unsaturated, optionally substituted heterocyclic residue, an alkylamine residue, an alkylamide residue or is connected to one of R3, R4, Y or R5, if present, with formation of an optionally substituted heterocyclic ring system which includes the nitrogen atom to which R6 is bonded and can be saturated or unsaturated and/or can contain further heteroatoms;
and their physiologically acceptable salts and stereoisomers, for the production of a pharmaceutical composition for the inhibition of angiogenesis and/or for the therapy and prophylaxis of cancer, osteolytic diseases such as osteoporosis, arteriosclerosis, restenosis, rheumatoid arthritis and ophthalmic disorders. It is particularly preferred in this case that, for the production of the pharmaceutical composition, compounds are employed such as are defined in one of the attached claims 1 to 11.